Spatial transcriptomic analysis of tumour-immune cell interactions in melanoma arising from congenital melanocytic nevus.

BACKGROUND: Studies on the interaction between tumour-infiltrating immune cells (TIICs) and tumour cells in melanoma arising from congenital melanocytic nevus (CMN) are lacking. OBJECTIVE: The aim of this study was to determine the intratumoral immune landscape of TIICs and tumour cells during invasion and metastasis. METHODS: Tissue specimens were obtained from patients with melanoma originating from CMN. Differential gene expression in melanoma cells and TIICs during invasion and metastasis was determined using spatial transcriptomics. RESULTS: As invasion depth increased, the expression of LGALS3, known to induce tumour-driven immunosuppression, increased in melanoma cells. In T cells, the expression of genes that inhibit T-cell activation increased with increasing invasion depth. In macrophages, the expression of genes related to the anti-inflammatory M2 phenotype was upregulated with increasing invasion depth. Compared to primary tumour cells, melanoma cells in metastatic lesions showed upregulated expression of genes associated with cancer immune evasion, including AXL and EPHA2, which impede T-cell recruitment, and BST2, associated with M2 polarization. Furthermore, T cells showed increased expression of genes related to immunosuppression, and macrophages exhibited increased expression of genes associated with the M2 phenotype. CONCLUSIONS: The interaction between melanomas arising from CMN and TIICs may be important for tumour progression and metastasis.

The efficacy and safety of low- versus high-fluence fractional picosecond Nd:YAG 1064-nm laser in the treatment of acne scars: A randomized split-face comparison study.

BACKGROUND: Differences in clinical efficacy based on the fluence of fractional picosecond laser treatment for acne scars are unknown. OBJECTIVE: To compare the efficacy and safety of low-fluence versus high-fluence fractional picosecond Nd:YAG 1064-nm laser treatment in acne scar patients. METHODS: In this 12-week, investigator-blinded, randomized, split-face study, 25 patients with moderate-to-severe acne scars received three sessions of high-fluence laser treatment (1.0 J/cm2 ) on one side of their face and low-fluence (0.3 J/cm2 ) on the other side every 4 weeks. Patients were assessed using acne scar counts, the scar global assessment (SGA), and the ECCA scar grading scale every 4 weeks. The histological analysis compared the acne scars obtained before and 4 weeks after treatment. RESULTS: At their last visit, 88.00% and 92.00% of the subjects achieved >30% reduction in scar counts on the low- and high-fluence sides, respectively, without a significant difference between the two sides. On both sides, the scar counts, SGA, and ECCA score significantly improved 4 weeks after the last treatment. Although the high-fluence side showed a greater reduction in scar counts (-66.73%) than the low-fluence side (-62.13%), the two sides had no significant difference in the grading scores. The high-fluence side showed significantly more severe pain and higher side-effect scores immediately and 4 weeks after treatment. Histological analysis revealed a significantly increased collagen, elastin, and vimentin expression after treatment on the low-fluence side. CONCLUSIONS: The low-fluence setting demonstrated comparable efficacy and superior safety in treating acne scars compared with the high-fluence setting.

Cyclin D1 and PRAME expression in distinguishing melanoma in situ from benign melanocytic proliferation of the nail unit.

BACKGROUND: Distinguishing benign lesion from early malignancy in melanocytic lesions of the nail unit still remains a diagnostic challenge, both clinically and histopathologically. While several immunohistochemistry (IHC) stainings have been suggested to help discriminate benign subungual melanocytic proliferation (SMP) and subungual melanoma in situ (MIS), the diagnostic utility of IHC staining for cyclin D1 and PRAME has not been thoroughly investigated in melanocytic lesions of nail unit. METHODS: This retrospective study included cases of benign SMP and subungual MIS confirmed by biopsy at Asan Medical Center from January 2016 to December 2020. Cases of melanocytic activation without proliferation and melanoma where dermal invasion was identified were excluded. Cyclin D1 and PRAME expression was assessed by counting proportion of melanocytes with nuclear positivity under 200x magnification. RESULTS: A total of 14 patients with benign SMP and 13 patients with subungual MIS were included in this study. 11 patients with benign SMP (71.4%) and 5 patients with subungual MIS (38.5%) showed > 60% nuclear immunostaining for cyclin D1, respectively. While 13 patients with benign SMP (92.9%) showed totally negative staining for PRAME, 10 patients with subungual MIS (76.9%) exhibited > 50% nuclear immunostaining for PRAME. Using the cutoff of 10%, PRAME exhibited good overall discrimination between benign SMP and subungual MIS (AUC = 0.849, 95% CI = 0.659-0.957). CONCLUSIONS: This study suggests that PRAME IHC staining as a reliable discriminator in distinguishing subungual MIS from benign SMP.

The Evaluation of Efficacy and Safety of A Radiofrequency Hydro-Injector Device for the Skin around the Eye Area.

In recent years, variable rejuvenation techniques, such as hyaluronic acid (HA) fillers and radiofrequency (RF) devices, have become popular. We evaluated the RF hydro-injector (RFHI) device that simultaneously delivers both a microneedle intradermal RF treatment and a HA filler injection to overcome the disadvantages of HA filler and RF devices alone. This study aimed to assess the efficacy and safety of the RFHI device for the rejuvenation of the periorbital area, including the lateral canthal lines (LCLs) and the infraorbital area. A total of 24 subjects were enrolled in this study and underwent 2 to 3 treatments using the RFHI device. The investigator's global assessment of the lateral canthal line (IGA-LCL) and the global esthetic improvement scale (GAIS) were used to evaluate the improvement in the LCL. Cutometer® was used to evaluate the skin's elasticity, and the Antera 3D image capture system® was used to evaluate the degree of wrinkles, roughness, and pore volume. At the 8 week follow-up after the first treatment session, both the IGA-LCL and GAIS showed significant improvement. The improvement in the wrinkles, roughness, and pore volume, measured by the Antera 3D image capture system®, was statistically significant. No serious adverse event was reported. This RFHI device, which delivers both microneedle intradermal RF treatment and HA filler injection, is effective and safe for periorbital rejuvenation.

A Case Report of Multiple Capillary Hemangioma in a Chronic Myeloid Leukemia Patient Taking Tyrosine Kinase Inhibitors.

A capillary hemangioma is a vascular tumor with small capillary sized vascular channel. Multiple capillary hemangioma in relation with drugs have been rarely reported. Here in, we report a case of multiple capillary hemangioma in patient diagnosed with chronic myeloid leukemia who received tyrosine kinase inhibitors (TKIs). Histopathological findings have shown capillary proliferation in the upper dermis, which is consistent with capillary hemangioma. Since TKIs can paradoxically activate the MEK/ERK pathway which is required for angiogenesis, we presumed that the lesions as the cutaneous side effects of TKIs.

Identification of genetic mutations related to invasion and metastasis of acral melanoma via whole-exome sequencing.

Many studies have analyzed the genes related to melanoma. However, only a limited number of studies have been conducted to identify the genes that are involved in the invasion and metastasis of acral melanoma (AM). Here, we attempted to investigate the genetic mutations associated with invasion and metastasis of AM. We analyzed five multi-regional samples of primary and metastatic AM and histologically normal tissue adjacent to the tumor (NAT) in two AM patients by whole-exome sequencing (WES). We identified single nucleotide variations and small indels present in tissue samples but not in saliva. We compared the sequencing results of superficial and deep lesions and primary and metastatic lesions of AM. We identified significantly deleterious mutations (SDM) that are likely to be related to invasion and metastasis of AM, respectively. SDM such as SKA3, MAST4, CNNM1, KIAA1549L, and SLC26A10 were found only in the deep lesion, but not in the superficial lesion. SDM present only in the metastatic lesion were ANO1, CPEB1, EP300, INADL, MAP1B, MAP7D1, MARCH6, NETO1, PRKCE, SBK1, TNRC6A, USP13, WDR74, and ZNF827. In conclusion, we applied multi-region WES to investigate possible pathogenic mutations related to invasion and metastasis in AM. Several genes including CNNM1, USP13, ZNF827, WDR74, CPEB1, and EP300 might be related to invasion and metastasis of AM. This study might facilitate the exploration of the evolutionary pathogenesis of advanced AM.

Efficacy and safety of neuronox® for lateral canthal lines: a phase I/III, multicenter, randomized, double-blind, active-controlled study.

INTRODUCTION: Neuronox® has not yet been investigated for its efficacy and safety in the treatment of lateral canthal lines (LCL). METHODS: This study was a randomized, double-blind, active drug controlled, multicenter, 16 week, Phase I/III study designed to determine the non-inferiority of Neuronox® compared to onabotulinumtoxin A (ONA) in the treatment of moderate to severe LCL. Thirty subjects in Phase I and 220 subjects in Phase III were randomized in a 1:1 ratio to receive a single treatment (24 U) of either Neuronox® or ONA. The primary endpoint of the Phase III study was the responder rate according to the proportion of subjects achieving Grade 0 (none) or 1 (mild) from 2 (moderate) or 3 (severe) in LCL severity at maximum smile as assessed by the investigators at Week 4. Additional efficacy endpoints and safety endpoints (adverse events) were also evaluated. RESULTS: The primary endpoint was achieved as the proportion of responders was 83% for both Neuronox® and ONA, thus, supporting the non-inferiority of Neuronox® compare to ONA. The two groups also showed no statistical differences in safety analyses. CONCLUSION: Treatment of moderate to severe LCL with Neuronox® was effective and well-tolerated.

Clinical characteristics and pathological depths of syringomas in 94 Korean patients.

BACKGROUND: Syringoma is a common benign tumor with eccrine origin that typically occurs on the face of middle-aged women. Laser ablation with CO2 laser or Er:YAG laser has been widely used in the clinical field, often leading to scars due to its deep location. This study aimed to investigate clinical characteristics and pathological depths of the lesions in syringoma patients. MATERIALS AND METHODS: Syringoma patients, pathologically confirmed at Samsung medical center (Seoul, Korea) from January 1996 to March 2019, were analyzed. Clinical characteristics such as the location of lesion, age, and sex, and pathological depths of the lesions were investigated, and univariable and multivariable analyses were done for these factors. RESULTS: Of total 94 syringomas, 17.0% were located on periocular area, 10.6% on forehead, 34.0% on head and neck areas excluding periocular area and forehead, and 38.3% on trunk and extremities. The mean depth of syringoma from the surface including stratum corneum to the deepest stromal location was 1174.14 ± 1142.95 µm for periocular area, 1055.93 ± 247.76 µm for forehead, 1488.06 ± 1217.36 µm for other areas of head and neck including scalp, and 1169.53 ± 349.2 for the lesions located at trunk and extremities including external genitalia. No significant correlation was observed from univariable analysis and multivariable analysis by age, sex, and site of lesion. CONCLUSION: Our findings offer valuable information of the mean depth of syringoma at different sites, which can be taken into consideration for successful treatment without adverse events such as scarring.

Is the survival rate for acral melanoma actually worse than other cutaneous melanomas?

It is still not clear whether the survival rate for acral melanoma (AM) is better or worse than that of cutaneous melanoma developed at other sites. We sought to evaluate the difference in survival depending on the primary tumor site of cutaneous melanoma. We retrospectively reviewed primary cutaneous melanoma cases diagnosed at Samsung Medical Center, a tertiary institution in Korea, from January 1995 to July 2017. The cohort consisted of 642 patients, with 389 non-acral cutaneous melanoma (NACM) patients and 253 AM patients. The AM patients had a higher percentage of stage 0 diagnoses than the NACM patients (31.6% vs 6.9%, respectively). The factors associated with overall survival were primary tumor site, sex, age, American Joint Committee on Cancer stage, surgery and medical treatment (P < 0.05). Non-acral sites showed worse survival in multivariable analysis (hazard ratio [HR], 1.457; 95% confidence interval [CI], 1.051-2.020; P = 0.0240). Among the NACM, melanomas on the trunk were associated with a higher risk of mortality compared with AM (HR, 1.883; 95% CI, 1.142-3.107; P = 0.0131). Acral melanoma was associated with a better prognosis than non-acral melanoma, specifically when located on the trunk, in Korean patients.

Evolutionary processes of melanomas from giant congenital melanocytic nevi.

Melanoma can develop in a congenital melanocytic nevus (CMN). In fact, a large CMN is associated with a high risk of developing melanoma. Although melanomas arising from CMNs are thought to have a pathogenesis distinct from conventional melanomas, no studies have been conducted on the evolution or tumor heterogeneity of CMN melanomas. We applied multi-region whole-exome sequencing to investigate the clonal nature of driver events and evolutionary processes in CMNs and melanomas arising from CMNs. In two patients, we observed an independent subclonal evolution in cancerized fields of CMNs and chromosome 8q amplification in both melanomas arising from CMNs. The amplification of MYC, located in chromosome 8q, was correlated with the percentage of tumor cells expressing high levels of MYC protein detected in melanoma cells by immunohistochemistry. Our analysis suggests that each CMN cell may evolve sporadically and that amplification of MYC might be a key event for melanoma development in CMNs.

The Important Factors Associated with Treatment Response in Laser Treatment of Facial Scars: A Single-Institution Based Retrospective Study.

BACKGROUND: There is increased interest in laser treatment of facial scars. OBJECTIVE: To determine the factors associated with treatment response. METHODS: We conducted an institution-based retrospective study by including the patients treated with laser for facial scars from 2012 to 2015. Treatment methods were determined with an algorithm according to individual scar characteristics. In each treatment session, either a 595-nm pulsed-dye laser or a non-ablative fractional laser was used, often in combination with a corticosteroid injection. We evaluated treatment responses based on the number of treatment sessions required to reach the treatment endpoint. Data were analyzed using multinomial logistic regression analysis to examine the association between treatment response and various factors of the scar. RESULTS: A total of eighty-four scars were analyzed. The onset of treatment (defined as the period between the injury and treatment initiation), used laser modality, and the location of the scar were all found to be significantly associated with treatment responses. Early implementation was more likely to provide better treatment response. Scars on the perioral area were more likely to be associated with worse treatment response. CONCLUSION: The important factors for the treatment response in facial scars were the location of the scar and the timing of the initiation of treatment. Such information can be used to predict treatment response and tailor the treatment plan to the patient, depending on scar characteristics.

Clinicopathologic features of 28 cases of nail matrix nevi (NMNs) in Asians: Comparison between children and adults.

BACKGROUND: Clinical distinction between nail matrix nevus (NMN) and subungual melanoma (SUM) can be challenging. More precise delineation of the clinicodermoscopic characteristics specific for NMNs is needed. OBJECTIVE: We sought to analyze the clinicopathologic features of childhood and adult NMNs and to propose clinicodermoscopic features that can aid in differentiating NMNs from SUM. METHODS: We retrospectively reviewed clinical, dermoscopic, and histologic findings of patients (20 children and 8 adults) in whom NMN was diagnosed between 2012 and 2015. RESULTS: Except for 2 cases of total melanonychia, the affected nails demonstrated longitudinal melanonychia sharply demarcated from the adjacent nail plate. Melanonychia was wider among children than among adults (P = .002). Nail dystrophy was more frequent in wider lesions (P = .028). Hutchinson's sign was observed in pediatric cases at the hyponychium and/or proximal nailfold cuticles. All hyponychial pigmentations demonstrated a longitudinal brush pigmentation pattern under dermoscopy. LIMITATIONS: This was a retrospective study of Asians in a single center. CONCLUSION: Our study is the largest case series to date of biopsy-confirmed NMNs. It highlighted important clinicodermoscopic differences between pediatric and adult NMNs. We propose that in pediatric cases of longitudinal melanonychia presenting as a sharply demarcated pigment band of even width, the presence of Hutchinson's sign with longitudinal brush pigmentation may favor a diagnosis of NMN over SUM.